3h-oxazolo-{8 4,5-6{9 -pyridine-2-one ester of 3-(-o-) (-5-)-o-lower alkyl aminophosphates and thiophosphates

ABSTRACT

New sulphur containing phosphorus compounds of pyrido-oxazole derivatives, their manufacture and use as pesticides are disclosed. The new compounds correspond to the formula   WHEREIN R1 represents halogen or nitro, R2 represents hydrogen or lower alkyl, R3 represents alkyl, alkoxy, alkenyloxy, alkynyloxy, phenyl, amino, monoalkylamino or dialkyl-amino, R4 represents alkyl, alkenyl or alkynyl, and X and Y each represent oxygen or sulphur.

United States Patent [191 Kristinsson et al.

[ Nov. ll, 1975 3H-0XAZOL0-I 4.5-6 l-PYRlDlNE-Z-ONE ESTER OF 3-(-O-l (-5-)-O-LOWER ALKYL AMINOPHOSPHATES AND THIOPHOSPHATES [75] Inventors: Haukur Kristinsson. Bottmingen;

Kurt Riifenacht, Basel. both of Switzerland I73] Assignee: Ciba-Geigy Corporation, Ardsley.

[ 2] Filed: Jan. 21, I974 {Ill Applv Nor. 435.343

Related U.S. Application Data i Division of Ser. No. 156983, June 25. I97], now Pat No. 3,808,2l8. which is a continuation-in-part of Ser. No. l55604June 22, l97l,abandoned.

[44] Published under the Trial Voluntary Protest Program on January 28. 1975 as document no.

[30] Foreign Application Priority Data June 264 1970 Snitlerlund 9702/70 i 1 US. Cl ..260/294.S C; 260/294.8 K; 260/297 B; 260/295 K; 260/296 H; 424/200 [51] Int. Clk' H C07D 213/65 Field of Search 260/2948 C [56] References Cited UNITED STATES PATENTS 2.984.669 5/196] Bruhler et nl. 260/307 C FOREIGN PATENTS OR APPLICATIONS 7]}.278 8/l954 United Kingdom 260/307 C Primary EmmUwr-Alun L. Rotmun AIM/THU)" Agem. u! Firm-Frederick H, Rubin; Karl F. Jorcln I ABSTRACT New sulphur containing phosphorus compounds of pyrido-oxuzole derivatives. their manufacture and use as pestieides are disclosed. The new compounds correspond to the formula R -{i S P/R3 na DESCRIPTION OF THE INVENTION The present invention relates to new organic phosphorus compounds, processes for their manufacture, insecticidal and acaricidal preparations that contain these new compounds and their use in combating animal and vegetable pests.

The new organic phosphorus compounds correspond to the formula if a l l CP-X 1) a la-ye 2 hurt wherein R, represents hydrogen, halogen or nitro, R represents hydrogen, methyl, chloromethyl or bromomethyl, R represents alkyl, alkoxy, alkenyloxy, alkynyloxy, alkoxyalkoxy, halogenalkoxy, phenyl, amino. monoalkylamino or dialkylamino, R, represents alkyl, alkenyl, alkynyl, alkoxyalkyl or halogenoalkyl and X and Y each represents oxygen or sulphur.

For R representing halogen, fluorine, chlorine, bromine or iodine, but especially chlorine or bromine, are suitable.

Alkyl, alkenyl or alkynyl chains that are possible for R and R, contain as lowe'r hydrocarbon radicals or as the hydrocarbon part of alkoxy, alkenyloxy, alkynyloxy, alkoxyalkoxy and alkylamino radicals R and R at the most 6, preferably at the most 4, carbon atoms and may be straight or branched.

Exemplary of such radicals are, interalia, methyl, ethyl, n-propyl, isopropyl, n-, i, sec.-, tert.-butyl, allyl, crotonyl, methallyl, propargyl, nbutynyl.

Particular importance attaches to compounds of the formula I wherein R, represents hydrogen, chlorine, bromine or nitro, R has the meaning given under formula 1 above, R represents an alkyl, alkoxy, alkenyloxy, alkoxyalkoxy, or halogenoalkoxy radical, each radical R containing at the most 4 carbon atoms, or a phenyl radical, amino radical or dialkylamino radical with 2 to 4 carbon atoms, R represents an alkyl, al kenyl, alkoxyalkyl or halogenoalkyl radical with at the most 4 carbon atoms and X and Y represent oxygen or sulphur.

The compounds of the formula I are manufactured by reacting an oxazolo(4,5 -b)pyridine derivative of the formula wherein A represents the halogenmethyl radical, the vinyl group or a l.2-dihalogenethyl radical, with a phosphorus compound of the formula HS P/R:s

P012 (IV) I optionally in the presence of an acid binding agent, or

with a salt thereof. In the formulae III and IV, the symbols R to R,, X and Y, have the meanings given for formula I.

The phosphorus compounds of the formula IV react with the oxazolo(4,5-b)pyridine derivatives of the formula III without further difficulties at temperatures between 0 and I20C, preferably at 10 to C. It is advisable to carry out the process according to the invention in the presence of a solvent or diluent that is inert towards the reactants. Possible solvents or diluents are primarily aliphatic ketones, such as acetone, methyl ethyl ketone; alkanols such as methanol, ethanol, isopropanol; esters, such as ethyl acetate; nitriles', N- alkylated acid amides; aromatic hydrocarbons, such as benzene, toluene and water, and mixtures of such solvents with water.

The reaction of a compound of the formula III, in which A represents halogen-methyl or l,2-dihalogenmethyl, with a compound of the formula IV takes place accompanied by the exchange of the, or a, halogen atom; in the process, the halogen atom in the l-position in the l,2-dihalogen-ethyl radical is exchanged. The reaction is therefore carried out by adding acid binding agents or with salts. especially with alkali metal salts and ammonium salts of the phosphorus compounds of the formula III. Preferred acid binding agents are the alkali metal hydroxides and carbonates; however, tertiary nitrogen bases can also be used. If A represents the vinyl group, the phosphorus compound of the formula IV adds on to the vinyl double bond.

As examples of possible starting materials of the formula III, the following may, inter alia, be considered for the process according to the invention: 3-chloromethyl-oxazolo 4,5-b]pyridin-2( 3H )-one 3-chloromethyl-oxazolo [4,5-b]pyridin-2( 3H l-thione 3-chloromethyl-6-chloro-oxazolo[4,5-blpyridin- 2(3H)-one 3-bromomethyl-6-chlorooxazolo[4,5-blpyridin- 2(3H)-one 3-chloromethyl-6-bromo-oxazolo[ 4,5 -b]pyridin- 2(3I-I)-one 3-chloromethyl-6-nitro-oxazolo[4,5-b]pyridin- 2(3H)-one 3-vinyl-oxazolo[ 4,5-b]pyridin-2( 3H )-one 3-vinyl-oxazolo[4,5-b]pyridin-2(3H)-thione 3-vinyl-6-chloro-oxazolo[4,5-b]pyridin-2( 3I-I)-one 3-vinyl-6-bromo-oxazolo[4,5-b]pyridin-2( 3I-I)-one 3-vinyl-6-nitro-oxazolo[4,5-b]pyridin-2(3H)-one 3-( l ',2'-dichloroethyl )-oxazolo[4,5-blpyridin-2- (3H)-one 3-( 1,2'-dibromoethyl)-oxazolo[4,5-b]pyridin- 3-(1 ,2 '-dichloroethyl)-oxazolo[4,5-b]pyridin-2(3 H)- thione 3-( l,2'-dibromoethyl )-oxazolo[4,5-b ]pyridin-2( 3H thione 3-( l ,2-dichloroethyl)-6-chloro-oxazolol4,5-blpyridin-2( 3H )-one 3-( l',2-dibromoethyl)-6-chloro-oxazolo[ 4,5-b1pyridin-2(3Hl-one 3-( 1 ',2'-dichloroethyl l-o-bromo-oxazolol4.5-b]pyridin-2( 3H )-one 3-( l ',2'-dibromocthyl )-6-bromo-oxazolo[4.5-blpyridin-2(3H)-one 3-( l ',2-dichloroethyl )-6-nitro-oxazolo[0,0-diethyldithiophosphoric pyridin-2(3H)-one 0,0-diethyl-S- lHl-onyH 3-[ l ',2-dibromoethyl )-6-nitro-oxazolo[ 4.5-blpyridin- 2(3H)-one The following thiophosphoric acids, thiophosphonic acids and thiophosphoric amides may be mentioned. inter alia as examples of phosphorus compounds of the formula IV: 0.0-dimethyl-dithiophosphoric acid (LU-dimethylmonothiophosphoric acid 0.0-diethyl-dithiophosphoric acid 0.0-diethyl-monothiophosphoric acid 0.(l-di-isopropyl-dithiophosphoric acid O-mcthyl-U-ethyl-dithiophosphoric acid U-mcthyl-() isopropyl-dithiophosphoric acid U-methyl-(J-isopropyl-dithiophosphoric acid 0.0-diallyl-dithiophosphoric acid 0.0-bis-( Z-methoxy-ethyl )-dithiophosphoric acid U,U-bis-( 2-ethoxy-eth \'l )dithiophosphoric acid (l.0-bis-( Z-chloroethyl J-dithiophosphoric acid U-methyl-dithio-methylphosphonic acid O-ethy]-dithio-methylphosphonic acid O-methyl-dithio-ethylphosphonic acid (l-cthyl-dithio-ethylphosphonic acid O-methyl-dithio-phenylphosphonic acid U-ethyl-dithio-phenylphosphonic acid U-methyl-thiophosphoric acid amide O-ethyI-thiophosphoric acid amide O-isopropyl-thiophosphoric acid amide O-methyl-thiophosphoric acid-methyl amide U-ethyl-thiophosphoric acid-methyl amide tl-methyl-thiophosphoric acid-ethyl amide ()-ethyl-thiophosphoric acid-ethyl amide O-methyl-thiophosphoric acid-dimethyl amide U-ethyI-thiophOsphoric acid-dimethyl amide O-methyl-thiophosphoric acid-diethyl amide O-ethyl-thiophosphoric acid-diethyl amide U-methyl-dithiophosphoric acid-dimethyl amide O-ethyl-dithiophosphoric acid-dimethyl amide 0-methyl-dithiophosphoric acid-diethyl amide 0-ethyl-dithiophosphoric acid-diethyl amide ()-isopropyl-dithiophosphoric acid-dimethyl amide The phosphorus compounds of the formula IV can be manufactured according to known processes.

The starting materials of the formula lll have not been described hitherto. The oxaZolo(4,5-b)-pyridine derivatives of the formula lll. in which A represents a halogen-methyl radical. are manufactured by converting an oxazolo(4,5-b)pyridine of the formula V u N H initially with formaldehyde into the corresponding 3- hydroxymethyl compound and reacting this with a halogenating agent to give the corresponding 3-chloromethyl resp. 3-bromoethyl-oxazolo[4.5-b]pyridine derivatives. As halogenating agents there may be used: thionyl chloride, phosphorus trichloride and phosphorus tribromide, phosphorus pentachloride and phosphorus pentabromide, phosphorus oxyhalides, etc.

since in the case of these oxazolol 4.5-b]pyridines there occurs no salt formation with the hydrogen halide that is split off. the addition of an acid binding agent can be dispensed with.

The starting materials of the formula Ill, in which A represents the vinyl group or a 1,2-dihalogen-ethyl radical, are obtained by reacting an oxazolo[4,5-b]pyridine of the formula IV with vinyl acetate in the presence of mercury salts of strong acids [H.Hopff et al., Helv.chim.Acta l8. l35-l40(1960] to give the corresponding 3-vinyl-oxazolol4,5-b1pyridine derivatives. It is also possible. moreover. to obtain such compounds by splitting off 3-(2'-hydroxyethyl) and 3-(2'-acetoxyethyl) derivatives) by heating or by reacting an oxazolol4,5-b]pyridine of the formula V with acetylene. The 3-( l ',2'-dihalogenethyl )-oxazolol4,5-blpyridine derivatives are then obtained by the addition of halogen. such as chlorine or bromine, to the vinyl group.

These reactions are carried out preferably in a solvent or diluent that is inert. or in solvent mixtures that are inert. towards the reactants. The hydroxymethyl group is introduced advantageously in an aqueous medium; the subsequent halogenation to the halogenmethyl group. likewise the addition of halogen to the vinyl group. in a halogenated hydrocarbon, such as chloroform. carbon tetrachloride. halogenated ethylenes and the like. In addition, aromatic hydrocarbons such as benzene. chlorobenzene and the like can also be used.

The reaction temperatures are in the range from 0 to l20C. The starting materials of the formula III are obtained in good yield and purity. They can be used directly for the reactions according to the invention without further purification.

The oxazolo[4.5-b]pyridine-2(3H)-ones represented by formula IV can be theoretically in a tautomeric form, represented by the formula lVa, as oxazolo[4,5- b]pyridine-2(4H)-ones. In this case, the acid NH-group would therefore be in the pyridine ring instead of in the oxazolo ring. The claimed compounds of the formula I could accordingly also be written as 4-substituted isomers, corresponding to an alternative formula la. However. since all claimed compounds and all their primary products always occur only in a single form, they are cited here for reasons of consistency and simplicity as 3-substituted isomers, both by formula and nomenclature. o

. C X (Iva,

1 i C X (Ia) R a 3 *8"? 2 Inca The compounds of the formula I are suitable for combating various animal and vegetable pests. They are particularly suitable for combating insects and representatives of the order Acarina. These active substances have a good to very good Contact action and ingested action combined with systematic action. and are of particular importance in combating insects that cat plants and suck the juice of plants. representatives of The active substances are non-toxic in the concentrations used for combating endoparasites, and are very well tolerated by domestic and farm animals.

The active substances of the formula I can be used as pure active substance or together with suitable carriers and/or additives. Suitable carriers and additives may be solid or liquid and correspond to the substances conventionally used in formulation technique.

The preparations according to the invention are manufactured in known manner by intimately mixing and grinding the active substances of the formula I together with suitable carriers, optionally with the addition of dispersing agents or solvents that are inert towards the active substances. The active substances can be in the form of and used in the following preparations: solid preparations:

dusting agents, scattering agents, granulates, coated granulates, impregnated granulated granulates and homogeneous granulates; liquid preparations:

a. active substance concentrates that are dispersable in water: wettable powders, pastes, emulsions;

b. solutions.

To produce dusts, scattering agents and granulates the active substances are mixed with solid carriers. Examples of carriers which can be employed are kaolin, talcum, bole, loess, chalk, limestone, ground limestone, Attaclay, dolomite, diatomaceous earth, precipitated silicic acid, alkaline earth silicates, sodium and potassium aluminium silicates (feldspar and mica), calcium and magnesium sulfates, magnesium oxide, ground synthetic plastics, fertilizers such as ammonium phosphates, ammonium nitrate, urea, ground vegetable products such as bran, bark dust, sawdust, ground nutshells, cellulose powder, residues of plant extractions, active charcoal, etc. These carriers can be used alone or admixed with each other.

The particle size of the carrier is, for dusts advantageously up to about 0.1 mm, for scattering agents from about 0.075 to 0.2mm, and for granulates 0.2 mm or coarser.

The concentrations of active substance in the solid preparations are usually from 0.5 to 80%.

To these mixtures can also be added additives which stabilize the active substance and/or non-ionic, anionic and cationic surface active substances, which for example improve the adhesion of the active ingredients on plants or parts of plants (adhesives and agglutinants) and/or ensure a better wettability (wetting agents) and dispersibility (dispersing agents). Examples of suitable adhesives are the following: olein/chalk mixture, cellulose derivatives (methyl cellulose, carboxymethyl cellulose), hydroxyethyl glycol ethers of monoalkyl and dialkyl phenols having to ethylene oxide radicals per molecule and 8 to 9 carbon atoms in the alkyl radical, lignin sulfonic acids, their alkali metal and alkaline earth metal salts, polyethylene glycol ethers (carbowaxes) fatty alcohol polyethylene glycol ethers having 5 to ethylene oxide radicals per molecule and 8 to l8 carbon atoms in the fatty alcohol moiety, condensation products of ethylene oxide/propylene oxide, polyvinyl pyrrolidones, polyvinyl alcohols, condensation products of urea and formaldehyde, and also latex products.

The water-dispersible concentrates of the active substance, i.e. wettable powders, pastes and emulsifiable concentrates, are agents which can be diluted with water to any concentration desired. They consist of active substance, carrier, optionally additives which stabilize the active substance, surface-active substances and anti-foam agents and. optionally, solvents. The concentration of active substance in these agents is 5 to Wettable powders and pastes are obtained by mixing and grinding the active substances with dispersing agents and pulverulent carriers in suitable apparatus until homogeneity is attained. Carriers are, for example, those mentioned for the solid forms of application. In some cases it is advantageous to use mixtures of different carriers. As dispersing agents there can be used, for example, condensation products of sulfonated naphthalene and sulfonated naphthalene derivatives with formaldehyde, condensation products of naphthalene or naphthalene sulfonic acids with phenol and formaldehyde, as well as alkali, ammonium and alkaline earth metal salts of lignin sulfonic acid, in addition, alkylaryl sulfonates, alkali and alkaline earth metal salts of dibutyl naphthalene sulfonic acid, fatty alcohol sulfates such as salts of sulfated hexadecanols, heptadecanols, octadecanols, and salts of sulfated fatty alcohol glycol ethers, the sodium salt of oleoyl ethionate, the sodium salt of oleoyl methyl tauride, ditertiary acetylene glycols, dialkyl dilauryl ammonium chloride and fatty acid alkali and alkaline earth metal salts.

Suitable anti-foam agents are silicones.

The active substances are so mixed, ground, sieved and strained with the additives mentioned above that, in wettable powders, the solid particle size of from 0.02 to 0.04 and in pastes, of 0.03 is not exceeded. To produce emulsifiable concentrates and pastes, dispersing agents such as those given in the previous paragraphs, organic solvents and water are used. Examples of suitable solvents are the following: alcohols, benzene, xylenes, toluene, dimethyl sulfoxide, and mineral oil fractions boiling between 120 and 350C. The solvents must be practically odorless, not phytotoxic, inert to the active substances and not readily inflammable.

Furthermore, the agents according to the invention can be applied in the form of solutions. For this purpose the active substance or several active substances of general Formula I are dissolved in suitable organic solvents, mixtures of solvents or in water. Aliphatic and aromatic and hydrocarbons, chlorinated derivatives thereof, alkyl naphthalenes, and mineral oils, alone or mixed with each other, can be used as organic solvents. The solution should contain the active substances in a concentration of from l to 20%.

The preparation according to the invention may also be mixed, for example, with fungicides, bactericides, fungistatics, bacteriostatics or nematocides, in addition to the insecticides and acaricides, in order to broaden the activity spectrum. The preparations according to the invention may also contain plant fertilisers, trace elements etc.

The content of active substance in the above described preparations varies from 0.l to and in this connection it should be mentioned that on application from an aircraft or by some suitable means of application, concentrations of up to 99.5% or even pure active substance may be used..

In the Examples that follow, preparations of the new active substances of the formula I are described. The parts denote parts by weight.

Dusting Agents The following substances are used for the manufacture of (a) a 57: and (b) a 2% dusting agent:

a. 5 parts of active substance of the formula l. e.g. 0.0-dimethyl-S-( 6-chloro-oxazolo( 4,5-b )-pyridin- 2( 3H )-onyl-( 3 )methy )dithiophosphate l parts of magnesium carbonate 85 parts of talcum b. 2 parts of 0,0-diethyl-S-(6-chloro-oxazolo(4,5-

b )pyridin-2( 3H )-onyl-( 3- )methyl )-dithiophosphate 1 part of highly dispersed silica 97 parts of talcum The active substances are mixed with the carriers.

Granulate The following substances are used to manufacture a 5% granulate:

5 parts of the active substance of the formula I. e.g.

0,0-diethyl-S-( 6-chloro-oxazolo( 4 ,5-b )pyridin- 2( 3H )-onyl-( 3- )methyl )-dithiophosphate 0.5 parts of epoxidised vegetable oil l part of highly dispersed silica 93.5 parts of kaolin (0.4 0.8 mm particle size) The active substance is mixed with the vegetable oil and the silica and dissolved in 6 parts of acetone. The resulting suspension is sprayed onto kaolin and the acetone subsequently evaporated in vacuo.

Wettable Powder The following constituents are used to manufacture a (a) 40%, (b) a 50%, (c) a 25% and (d) a l0% wettable powder:

a. 40 parts of active substance of the formula I, e.g.

0,0-dimethyl-S-( oxazolo( 4,5-b )pyridin-2( 3H)- onyl-( 3 )-methyl )-dithiophosphate 5 parts of the sodium lignin sulphonate I part of the sodium dibutyl naphthyl sulphonate 54 parts of silica b. 50 parts of the active substance of the formula I,

e.g. 0,0-diethyl )-S-(oxazolo( 4,5-b)pyridin-2( 3H onyl( 3 )-methyl-clithiophosphate 5 parts of alkylaryl sulphonate (Tinovetin B") 10 parts of calcium lignine sulphonate l part of Champagne chalk-hydroxyethyl cellulose mixture (lzl) parts of silica 14 parts of kaolin; c. parts of the active substance of the formula 1,

Emulsifiable concentrate The following constituents are mixed together to manufacture (a) a l0% and (b) a 20% emulsifiable concentrate:

a. 10 parts of active substance of the formula I, e.g.

0.0-dimethyl-S-[ 6-chloro-oxazolo[ 4 .5-b -pyridin- 2( 3H )-onyl-( 3 )-methyll-dithiophosphate I0 parts of a composite emulsifier (fatty alcohol polyglycolether and ethyl arylsulphonate) 40 parts of dimethylcyclohexylphthalate 40 parts of tetralin;

b. 20 parts of active substance of the formula I, e.g.

0.0-diethylS-l6-chloro-oxazolo[4.5-bl-pyridin- 2( 3H )-onyl-3 )-methyl ]-dithiophosphate 20 parts of dioxane 10 parts of a composite emulsifier (fatty alcohol polyglycolether and alkylaryl sulphonate) 50 parts of tetralin.

This concentrate can be diluted with water to form emulsions of any desired concentration.

Spray The following constituents are used to manufacture (a) a 5% and (b) a 2 7: spray:

a. 5 parts of active substance of the formula I, e.g.

0,0dimethyl-S-[ oxazolo[ 4,5 b ]pyridin-2( 3H onyl-( 3 )-methyl]-dithiophosphate l part of epichlorohydrin 94 parts of petroleum ether (boiling limits b. 2 parts of active substance of the formula I. e.g.

0,0-dimethyl-S-[6-chloro-oxazolo[4.5-b1-pyridin- 2( 3H )-onyl-( 3 )-methyl l-dithiophosphate 3 parts of 4.4-dichlorodiphenyl-trichloroethane 95 parts of kerosene.

These solutions are sprayed with a pressure sprayer. Anti-helminthic preparations of the new phosphorus compounds of the formula I are described herewith below. The parts denote parts by weight.

Active substance concentrate in paste form Such semisolid or oily active substance concentrates have, for example. the following composition:

a. 40 parts of active substance of the formula I, e.g.

0,0-diethyl-S-[ 6-chloro-oxazolo[ 4,5-b1pyridin- 2( 3 H )-only-( 3 )-methyl]-dithiophosphate 10 parts of bolus alba 2 parts of sodium lignin sulphonate 0.2 parts of sodium benzoate 10 part of carboxymethyl cellulose 46.8 parts of water; b. 30 parts of active substance of the formula I, e.g.

0,0-bis(2'-chloroethyl)-S-[oxazolo[4,5-b1-pyridin-2( 3H )-onyl-( 3 )-methyl]-dithiophosphate 70 parts of ground-nut oil. The active substances are very finely ground with the carriers, dispersants and other additives (particle size 5-10 microns).

Powder concentrate The following substances are used to manufacture (a) a 50% and (b) a 25% powder concentrate:

a. 50 parts of active substance of the formula I. e.g.

0,0-diethyl-S-[oxazolo[ 4,5-b ]pyridin-2( 3H )-onyl- 3 )-methyl 1 -dithiophosphate 3 parts of polyoxyethylene-sorbitan-monooleate 3 parts of sodium lignin sulphonate 44 parts of bolus alba: b. 25 parts of active substance of the formula I, e.g.

0,0-diethyl-S-[oxazolo[4.5-b]pyridin-2( 3H thione- 3-y-methyl l-dithiophosphate 8 parts of polyvinyl pyrrolidone 3 parts of dodecylbenzenesulphonate 39 parts of diatomaceous earth 30 parts of bolus alba.

1 l The indicated active substances are applied to the carriers. for example in the form of acetonic solutions. The dispersants and wetting agents are added subsequently and the concentrate is ground to homogeneity.

EXAMPLE 1 a. 109 Grams of oxazolol4.5-b]pyridine-2-(3H)-one J. Frazer and E. Tittenser. J. Chem. Soc.(London) 1957. 4625 are stirred in a mixture of I g of approx. 37% aqueous formaldehyde solution and 600 ml of water for one-half hour at room temperature and for one-half hour at 50-60 "C. After cooling. filtration and drying to filtrate. 126 g of 3-hydroxymethyloxazolol4.5-b]-pyridine-2( 3H)-one are obtained (mp.

155C. with decomp.).

b. 126 Grams of 3-hydroxymethyl-oxazolo[4,5- blpyridine-2-(3HJ-one are suspended in 1200 ml of chloroform. I26 Grams of thionyl chloride are run in rapidly. the mixture is stirred initially for half an hour at room temperature. then for 3 hours at 60C. cooled and the undissolved impurities are filtered off. The filtrate is evaporated to dryness in a water jet vacuum. the residue mixed with petroleum ether and filtered. to yield I26 g of 3-chloromethyl-oxazolo[4.5-blpyridine- 2(3Hl-one (m.p. l09l l lC).

c. 18.5 Grams of 3-chloromethyl-oxazolo[4.5-b1pyridine-2(3H)-one and 21 g of the ammonium salt of 0,0- dimethyldithiophosphate are stirred in 100 ml of acetone for 4 hours at C. 100 Millilitres of water are added and the acetone is distilled off in a water jet vacuum at 35C. The crystals that have separated out are filtered off and recrystallised from methanol. to yield 20 g of 0,0-dimethyl-S-[oxazolol4,5- b]pyridine-2( 3H )-onyl-( 3 l-methyl]-dithiophosphate (m.p. 70-7lC).

Calc. N 9.] 5 P l0.l S 20.9 12 Found N 9.3 P S 20.9 '1

EXAMPLE 2 b pyridine-2( 3H )-onyl( 3 )-methyl dithiophosphate (m.p. 8687C).

Calc. c 39.51 H 4.53 N 8.33 P 9.21 1 s 19.1:1 '12 Found c 39.55 H 4.55 N 8.48 P 9.19 s 19.2. a;

EXAMPLE 3 63 Grams of the potassium salt of 0.0-bis(2- methoxyethyl)-dithiophosphoric acid and 37 g of 3- chloromethyl-oxazolo [4.5-b]pyridine-2(3H)-0ne are stirred in 300 ml of acetone for 4 hours at 40C. The solvent is then distilled off in a water jet vacuum. the residue treated with 300 ml of water. and the oil that has separated out is taken up in ether. The ether solu- Cale. Found EXAMPLE 4 49 Grams of O-ethyl-dithio-phenylphosphonic acid and 37 g of 3-chloromethyl-oxazolol4.5-b1pyridine- 2(3H)-one are dissolved in 200 ml of acetone. While stirring. a solution of 9 g of sodium hydroxide in 40 ml of water is added dropwise and the mixture is then heated for 4 hours to 35C. The acetone is distilled of in a water jet vacuum. the residue treated with 200 ml of water and extracted with ether. The ethereal extract is washed until neutral. dried and distilled off. to leave a rapidly congealing oil. Recrystallisation from 300 ml of methanol yields. 37 g of O-ethyl-S-[oxazolo[4.5- b]pyridine-2( 3H )-onyl-( 3 l-methyll-dithio-phenylphosphate Gale. (7 49.16 H 4.13 N 7.64 P 8.47 5 17.5001 Found 49.10 4.211 7.61 8.66 17.2110;

EXAMPLE 5 a. 204 Grams of oxazolol4,5-b]pyridine-2(3H)-one are dissolved in 1500 ml of dimethylformamide. At 20-25C. l 1 l g of chlorine are introduced into the solution within 2 hours. The mixture is further stirred for 1 hour and poured into 3 litres of ice water. The product that has crystallised out is filtered off, washed and dried. 2| 2 Grams of 6-chloro-oxazolo [4.5-blpyridine- 2-(3H)-one (m.p. l87l88C) are obtained.

b. I35 Grams of 6-chloro-oxazolo[4.5-b]pyridine-2- (3H )-one. 800 ml ofwater and I60 g ofan approx. 37% aqueous formaldehyde solution are stirred for one-half hour at room temperature and then for 2 hours at 5060C. The mixture is cooled. the precipitate that forms filtered off, the residue washed with ice water and dried at 40C in a water jet vacuum. 148 Grams of 3-hydroxymethyl-6-chloro-oxazolo[4,5-b1pyridine- 2(3H)-one (m.p. l38C. with decomp.) are obtained.

c. 200 grams of thionyl chloride are rapidly run into a suspension of 240 g of B-hydroxymethyl-6-chlorooxazolo [4.5-b]pyridine-2( 3H )-one in l200 ml of chloroform. The mixture is stirred for one-half hour at room temperature, then for 1 hour at 60C. The by this time clear solution is evaporated to dryness in a water jet vacuum. the residue treated with petroleum pyridine-2(3H)-one (m.p. 104-l06C) are obtained.

d. 44 Grams of 3-chloromethyl-6-chlorooxazolo[4,5-b]pyridine-2(3 H)-one and 49 g of the ammonium salt of 0.0-diethylmonothiophosphoric acid are stirred in 300 ml of acetone for 4 hours at 60C. The acetone is distilled off in a water jet vacuum and the residue treated with 300 ml of water. The crystal- 13 line precipitate that has formed is filtered off and recrystallised from methanol. 42 Grams of 0.0-diethyl-S- [o-chloro-oxazolol 4.5-blpyridine-2( 3H )-onyl-( 3 l4 oxazolol4.5-b]pyridine-2( 3H)-one are dissolved in ISO ml of acetone. A solution of 6.5g of sodium hydroxide in 65 ml of water is then added dropwise and the mixmethyl]-dithiophosphate are obtained (m.p. ture is stirred for 4 hours at 40C. 5 The acetone is thereafter distilled off in a water jet vacuum. 300 ml of water are added and the oily crystalline precipitation that forms is taken up in ether. The Etta- H jg N P 5 ether solution is washed with sodium bicarbonate solut1on and with water. Recrystall1sat1on once from a 10 small amount of methanol yields 22 g of ().O-bis-(2- chloroethyl )-S[ o-chloro-oxazolo- 4 .5 -b ]pyridine- EXAMPLE 6 2( 3H)-onyl-( 3 )-methyll-dithiophosphate (m.p. A solution of 238 g of 3-chloromethyl-o chloro- 71O 73)C' Cale. c 311.114 H 2.76 N 6.411 P 7.09 3 14.69 c1 24.311 w Found 311.23 2.79 6.211 6.96 14.72 24.29: t.

oxazolol4.5-h]pyridine-2(3H)-one in 500 ml of ace- 3U X M 9 tone is slowly added dropwise to a suspension of 255 g of the potassium salt of 0.0-dimethyldithiophosphoric acid in 500 ml of acetone. The temperature gradually rises to 32C and the mixture is further stirred for 4 hours at C. The solvent is thereafter stripped off in a water jet vacuum. the residue treated with [00 ml of water. and the oil that has separated out is taken up in ether. The ether solution is washed with sodium hydrogen bicarbonate solution and with water and the ether is dried and distilled. The residue congeals to crystalline form. Recrystallisation from 500 ml of methanol yields, 198 g of 0,0dimethylS-[ 6-chloro-oxazolo[4,5-

Grams of O-methyl-dithio-phenylphosphonic acid are dissolved in 200 ml of acetone. A solution of 9 g of sodium hydroxide in 400 ml of water is then added dropwise. Thereafter 44 g of EX. 5c) are introduced and the reaction mixture is stirred for 4 hours at 35C. The acetone is then distilled off in a water jet vacuum. the residue treated with 200 ml of water and extracted with ether. The ethereal extract is washed until neutral, dried and the ether distilled off to leave an oil that crystallises gradually.

Recrystallisation from 500 ml of methanol yields 28 g of 0-methyl-S-[6-chloro-oxazolo{4,5-b pyridine]- b"'-23H- h'-'h' z met 1] lophosphne (m p 2(3H)-onyl-(3)-methyl]-d1th1o-phenylphosphate (m.p.

CUIC. c 31.72 H 2.96 N 8.23 P 9.11 s 18.8: 61 10.41% Found 31.33 2.95v 8.28 8.89 121.53 111.635;

lO5-lO7C).

Calc. C 43.47 1-1 3,13 7.24 P 8.02 5 16.57 09.17 71 Found 43.41 3.24 6.97 8.03 16.52 9.25 /1 EXAMPLE 7 EXAMPLE 10 166 Grams of the potassium salt of 0.0-diethyl-dithiophosphoric acid and 135 g of 3-chloromethylo-chlorooxazolol4.5-b]pyridine-2( 3H)-one are dissolved in 800 ml of acetone. The temperature of the reaction mixture slowly rises to 33C. 600 Millilitres of water are then added and the bulk of the acetone is distilled off in a water jet vacuum at 35C. The oil that has initially seta. 204 Grams of oxazolo 4,5b pyridine-2-(3H)-one are dissolved in l500 ml of dimethylformamide. 264 Grams of bromine are slowly added dropwise at room temperature. the mixture is stirred for l hour and poured into 9 litres of ice water. The crystalline product that forms is filtered off and dried in vacuo at C yielding 249 of 6-bromo-oxazolol 4.5-

tled out congeals to crystalline form. Recrystallisation r g o o from 500 ml of methanol yields 170 g of 0,0-diethyl-S- g g g [6-Cl'llOfO-OX8ZOlOl4.5-b]pyridirl-2(3H)-Only-(3)- 7 mm 0 lmethy]l dithiophosphate (mp. o 2c (3H)-one. 900 ml of water and 100 g of an approx.

Cale. C 35.82 H 3.83 N 7.60 P 8.42 5 17.39 09.62 '71 Found 35.85 3.1m 7.64 8.3l 17.34 9.97 "/1 37% aqueous formaldehyde solution are stirred for EXAMPLE 8 one-half hour at room temperature and then for l hour 42 Grams of 0.0-bis-(2-chloroethyl)-dithiophosphoric acid and 35 g of 3-chloromethyl-6-chlorounder reflux. The mixture is cooled. the precipitate that forms is filtered off, washed with ice water and dried at 40C in vacuo. yielding l84 g of 3-hydroxymethyl-6- bromoxazo1o[4.5-b]pyridine-2(3H)-one (decomp. at 130C; with splitting off of formaldehyde).

c. 133 Grams of thionyl chloride are run rapidly into a suspension of 183 g of 6-bromo-oxazolo[4.5-b]-pyridine-2( 3H )-one in 1500 ml of chloroform. The mixture is stirred for one-half hour at room temperature and then for 2 hours at 60C. The by now clear solution is evaporated to dryness in a water jet vacuum, the residue mixed with petroleum. filtered off and dried, yielding 192 g of 3-ch1oromethyl-6-bromo-oxazolo[4,5- b]pyridine-2(3H)-one (m.p. 129130C).

d. 116 Grams of 3-chloromethyl -6-bromo-oxazo1o [4,5-b]pyridine-2( 3H )-one and 1 19 g of the potassium salt of 0,0-diethyldithiophosphoric acid are stirred for 4 hours at 35C in 600, 1 of acetone. The acetone is then distilled off in vacuo and the residue treated with 600 ml of water. The oil that has separated out congeals to a crystalline form after it has been thoroughly stirred.

Recrystallisation from methanol yiels 136 g of 0,0-

diethyl-S-l 6-bromo-oxazolol 4,5-b]pyridine-2( 3H ony1-(3)-methyll dithiophosphate (m.p. 98 99C).

Cale. C 31.97 H 3.42 N 6.78 P 7.51 5 15.52%

Found 32.09 3.37 6.87 7.36 15.4856 (.alc. B1 19.33 '7: Found 19,81 .7

EXAMPLE 11 Calc. N 7.27 8 16.64 P 8.05 91 Found 7.3 16.4 7.9 92

EXAMPLE 12 56 Grams of the potassium salt of di-isopropyl-dithiophosphoric acid and 53 g of 3-ch1oromethy1-6-bromooxazo1o[4,5-b]pyridine-2(3H)-one are stirred in 300 ml of acetone for 4 hours at 35C. The acetone is distilled off a water jet vacuum, the residue treated with 300 ml of water, and the oil that has separated out taken up in ether. The ethereal solution is washed with sodium bicarbonate solution. dried and the ether distilled off. The residual oil is dissolved in 120 ml of methanol. 62 Grams of 0,0-diisopropyl-S-[6-bromooxazolo[4,5-b] pyridine-2-( 3H )-ony1-( 3 )-methyl dithiophosphate (m.p. 6567C) crystallise on coolmg.

Cale. C 35.37 H 4.11 N 6.3 P 7.03 S 14.53% Found 35.35 3.95 6.31 7.02 14.56% Cal:v Br 18.28 7% -continued Found 19.06 "1 By using 55 g of the potassium salt of 0,0-dia1lyldithiophosphoric acid and proceeding in a manner analogous to the above Example. 42 g of 0,0-diallyl-S-[6- bromo-oxazolol4,5-b]pyridin-2( 3H )-ony1-( 3 a. 152 Grams of oxazolo 4,5-b pyridine-2( 3H )-thione [T. Takahashi & F. Yoneda, Pharm. Bull. (Tokyo) 5, 350 (1957)] in a mixture of g of a 377: aqueous formaldehyde solution and 600 ml of water are stirred for one half hour at room temperature and subsequently for 2 hours at 60C. After cooling, filtration and drying the filtrate, g of 3 hydroxymethyl- 0xazolo[4,5-b]pyridin-2(3H)-thione are obtained (no real melting point; splitting off of formaldehyde at 110C).

b. 180 g of 3-hydroxymethyl-oxazolol4,5-blpyridin- 2( 3H)-thione are suspended in 1500 ml of chloroform. 167 Grams of thionyl chloride are run in at room temperature, the mixture is stirred for half an hour at the same temperature then gradually heated to 60C and maintained at this temperature for 2 hours. The by now clear solution is evaporated to dryness, the residue stirred with petroleum ether and filtered, yielding g of crude 3-chloromethyl-oxazolo[4,5-b]pyridin-2( 3H thione (mp. 120 123C).

c. 95 Grams of the potassium salt of 0,0-diethyldithiophosphoric acid and 70 g of 3-chloro-methy1-oxazolo 4,5-b pyridine-2(3H)-thione are suspended in 800 m1 of acetone. The suspension is stirred for 4 hours at 35 40C, then the acetone is distilled off in a water jet vacuum and the residue treated with 800 ml of water. The oil that has initially separated out congeals to crystalline form. Recrystallisation from 400 ml of methanol yields 87 g of 0.0-diethyl-S-[oxazolol4,5-b]pyridin- 2( 3H)-thione-3-yl-methyl ]dithiophosphate (m.p. 64 66C).

Cale. C 37.70 H 4.3: N 7.99 P 11.215 5 27.45% Found 37.43 4.18 7.91 8.59 27.78%

EXAMPLE 14 17 tallised directly from 400 ml of methanol. to yield 46 g of -methyl-S-[6-chloro-oxazolo-[4,5-b]pyridin- 2( 3H )-onyl-( 3 )-methyl1-dithio-methyl-phosphonate (m. p. 77 79C).

18 the onset of turbidity. On cooling, 83 g of pale yellow 3-chloromethyl-6-nitro-oxazolo[4,5-b1pyridin- 2(3l-l)-one crystallise (m.p. l07 109C).

d. 46 Grams of 3-chloromethyl-6-nitro-oxazolo[4,5-

ctac. c 33.28 H 3.111 N 8.63 P 9.56 5 19.74 c1 111.9: Found 33.56 2.9 11.51 9.54 19.47 11.110

b 'ridin-Z 3H -one and 38 of the ammonium salt of EXAMPLE l g 22 Grams of 3-chloromethyl-o-chloro-oxazolol4.5- b] pyridine-2(3H)-one and l9 g of O-methyl-N,N- dimethyl-dithiophosphoric acid amide are dissolved in l50 ml of acetone. A solution of 5 g of sodium hydroxide (solid) in 25 ml of water is then added dropwise and the mixture is stirred for 4 hours at 40C. The bulk of the solvent is subsequently distilled off in a water jet vacuum and the residue treated with 100 ml of water. The oil that has separated out is crystallised at once. Recystallisation from methanol yields 25 g of O-methyl- N.N-dimethyl-S- l 6-chloro-oxazolo[ 4.5 -b ]-pyridin- 2( 3H )-onyl-( 3 )-methyl l-clithiophosphoric amiclate (m.p. 89 91C).

Calc. Found 0.0-dimethyl-dithiophosphoric acid are dissolved in 150 ml of acetone and the solution is stirred for 4 hours at 40C. The solvent is then distilled off in a water jet vacuum at 40C. the residue is treated with water and the oil that has separated out is taken up in ether. After being repeatedly shaken out with sodium bicarbonate solution and with water, the ether solution is dried and the solvent distilled off. The residual oil crystallises after a time. Recrystallisation twice from 10 times the amount of methanol yields 26 g of 0.0-dimethylS-[6- nitrooxazolol 4,5-blpyridin-2( 3H )-onyl-( 3 )-methyl dithiophosphate (m.p. 6 l-63C Cl 10.0254 10. l 8% EXAMPLE 16 a. 272 Grams of oxazolo[4,5-b]pyridine-2-(3l-l)-one are introduced at 5 to 5C into 800 ml of concentrated sulphuric acid. Thereafter 400 ml of fuming nitric acid are added dropwise at 0l0C and the mixture is left to stand for 3 to 4 days at room temperature. The reaction mixture is then poured onto 3 kg of ice. the precipitated nitration product filtered off and recrystallised frorn ethanol/water to yield l4l g of the pale yellow 6-nitro-oxazolo[4,5-b]pyridin-2(3H)-one (m.p.225C accompanied by previous conversion at 200C).

b. 90 Grams of 6-nitro-oxazolo[4,5-b]pyridin-2( 3H)- oneare suspended in 550 ml of water. 1 l0 Millilitres of an approx. 37 76 aqueous formaldehyde solution are then added and the mixture is stirred for one half hour at room temperature and then for 2 hours at 60C. The resulting paste is cooled, filtered and the filter cake washed with cold water. After a thorough drying in vacuo at 40C. 102 g of pale yellow 3-hydroxymethyl- 6-nitro-oxazolo[4,5-b]pyridin-2( 3H )-one are obtained. which decomposes from 140C accompanied by splitting off of formaldehyde.

c. I06 Grams of 3-hydroxymethyl-6-nitro-oxazolo [4,5-b]pyridin-2( 3H)-one are suspended in 750 ml of chloroform 5 milliliters of dimethylformamide are added and 100 g of thionyl chloride are then run in at room temperature. With gradual heating, the reaction commences accompanied by vigorous development of gas. After the reaction has subsided, the mixture is boiled for 1 hour under reflux and all volatile components are then distilled off in a rotary evaporator at 50C. The residue forms a viscous oil or a crystalline crust. It is dissolved in I50 ml of ethyl acetate, the solution is treated with 75 ml of petroleum ether and filtered over animal charcoal. The clear filtrate is treated at 45C with petroleum ether (approx. [50 ml) until Calc. Found EXAMPLE l7 a. To 344 g of vinyl acetate are added initially 5.6 g of mercury acetate and then 0.75 g of sulphuric acid monohydrate. 65-5 Grams of oxazolo[4,5-b]pyridine- 2-(3H)-one are then introduced and the mixture is heated for 7 hours under reflux. The mixture is then cooled, filtered until clear and concentrated in a rotary evaporator. The oily residue is treated with ice. then crystallised. Recrystallisation from aqueous methanol yields 54 g of 3-vinyl-oxazolo{4.5-b]pyridin-2(3H)-one (m.p. 55-57C).

b. 32 Grams of 3-vinyl-oxaz0lo[4,5-b]pyridin- 2(3l-l)-one and 45 g of diethyl-dithiophosphoric acid are disolved in l50 ml of toluene and boiled under reflux for 8 hours. The reaction mixture is then cooled, diluted with ether and shaken out with sodium bicarbonate solution and with water. The ethertoluene solution is dried and the solvent is distilled off. The residual oil crystallises slowly. Recrystallisation from ml of methanol yields 37 g of 0,0-diethyl-S-[oxazolo[4.5- b]pyridin-2( 3H )-onyl-( 3 )-ethyl-( l )l-dithiophosphate (m.p. 39-4lC).

a. To a solution of 32.4 g of 3-vinyl-oxazolo[4.5- b]pyridin-2(3l-l)-one in 200 ml of carbon tetrachloride are added slowly dropwise while cooling with ice at 0l0C 32 g of bromine dissolved in I00 ml of carbon Cale. Found b. 64 Grams of 3-( l',2'-dibromo-ethyl )-oxazolo[4,5- b]pyridin-2( 3H )-one and 37 g of the ammonium salt of 0,0-dimethyl-dithiophosphoric acid are dissolved in 250 ml of acetonitrile and stirred for 3 hours at 60C. The bulk of the solvent is then distilled off in a water jet vacuum and the residue is treated with 200 ml of water. The oil that has separated out is taken up in ether. the ether solution is washed with sodium bicarbonate solution and with water. dried. and the ether distilled off. The residue crystallises. Recrystallisation from 55 ml of methanol yields 30 g of 0.0-dimethyl-S-[oxazolo-[4.5- b]pyridin-2( 3H )-onyl-( 3 H 2-bromo-ethyl H l')]- dithiophosphate (m.p. 78-80C EXAMPLE a. To a solution of 98 g of 3-vinyl-t-chloro-oxazolo- 14,5-b1pyridin-2t3Hl-one and 0.2 g of hydroquinone in 800 ml of carbon tetrachloride are slowly added dropwise while cooling with ice at 010C 80 g of bromine dissolved in 200 ml of carbon tetrachloride. The reaction mixture is filtered until clear and evaporated in a rotary evaporator. The crystalline residue is triturated with 300 ml of petroleum ether and filtered to yield 161 g of 3-( l',2'-dibromoethyl)-6-chloro-oxazolo[4.5- blpyridin -2(3H)-one (m.p. 7l73C).

Cale. Found Br 44.9 Br 44.5

N 7.8% CI 10.1 K855i Cale. c 311.1111 1-1 3.03 N 7.11: P 7.76 5 mos Br 211.1121; Found 311.19 3.113 7.06 7.114 111.1111 211.1 2 .1

out is taken u in ether, the ether solution is washed EXAMPLE 19 p a. As in Example 16. 344 g of vinyl acetate, 5.6 g of mercury acetate, 0.75 g of sulphuric acid monohydrate and 85.3 g of 6-chloro-oxazolo[4.5-b]pyridine-2- (3Hl-one are mixed together and the reaction mixture is stirred for 12 hours at C. The mixture is then fil- Calc. C 31 Found Cl 1 8.1% I 8.09}

Calc. Found with sodium bicarbonate solution and with water. dried, and the ether distilled off. 86 Grams of a pale yellow. non-distillable oil are obtained. which consists largely of 0.0-diethyl-S-[6-chloro-oxazolo[4.5-b]pyridin-2( 3H )-onyl-( 3 H 2'-bromoethyl H 1 l-dithiophosphate EXAMPLE 21 a. Proceeding in a manner analogous to that described in Example 17, 700 g of vinyl acetate. 1 ml of sulphuric acid monohydrate and 214 g of 6-bromooxazol0[4.5-b]-pyridine-2(3H)-one are reacted under reflux. The reaction mixture is then filtered hot until clear and the filtrate evaporated to dryness in vacuo. The residue is suspended in water and filtered. 190 Grams of crude product are obtained. Recrystallisation from 1100 ml of ethanol yields 147 g of 3-vinyl-6- b. 39 Grams of 3-vinyl-6-chloro-oxazolo[4.5-blpyrii' %T '?f? P)" -P- din-2(3Hl-one and 45 g of 0,0-diethyl-dithiophosphoric acid are dissolved in 150 ml of toluene and boiled under reflux for 8 hours. The reaction mixture is Cale, c 3W5 H 33. N 11.6% cooled. diluted with ether, shaken out with sodium bi- Found c 40.: H 2.1 Br 33.8 N 11.601 carbonate solution and with water. dried. and the solvent distilled off. The residual oil crystallises. Recrys- 6U tallisation from ml of methanol yields 61 g of 0.0- b. 38 Grams of 0.0-dimethyl-dithiophosphoric acid diethyl-S-[6-chloro-oxazolo[4,5-b]pyridin-2(3H)- and 48 g of vinyl-6-bromo-oxazolo[4.5-blpyridinonyl-(3)-ethy1-(l')]-dithiophosphate (m.p. 4547C). 2(3H)-one are dissolved in ml of anhydrous ben- Cale. c 37.05 H 4.22 is 7.31 P 8.10 5 16.75 c1 9.2a

zene and boiled under reflux for 8 hours. The reaction mixture is cooled. diluted with ether and shaken out with sodium bicarbonate solution. The product is crystallised from the ether solution filtered and recrystallised from 900 ml of methanol to yield 56 g of 0,0- dimethyl-S-[ 6-bromo-oxazolo[ 4,5-b]pyridin-2( 3H onyl( 3 )-ethyl-( l ]-dithiophosphate (mp.

lll l7C).

22 from 250 ml of ethanol to yield 4] g of pale yellow 3- vinyl-o-nitro-oxazolo[ 4,5-b]pyridin-2( 3H )-one (m.p. l07l()9C).

b. 38 Grams of 0,0-dimethyl-dithiophosphoric acid 5 and 41 g of 3-\'inyl-6-nitro-oxazolo[4.5-b1pyridin- 2(3H)-one are reacted as in Example 21b. Recrystallisation twice from 150 ml of methanol yields 19 g of 0,0- dimethyl-S-[6-nitro-oxazolo[4,5b]pyridin-2( 3H Calc. c mm H 3m N 7.01 P 7.77 5 16.06 Br 3mm; Found 6 mm H 3m N 7.01 P 7.55 s l6 |7 Br 20.2w

l: onyl (3)-cthyl-( l')]-dith iophosphate (m p. EXAMPLE l07-l 10C; mixed melting point with starting material a. To 240 g of vinyl acetate are added successively 77 80C).

3.6 g of mercury acetate. 0.45 g of sulphuric acid monohydrate and 54 g of o-nitro-oxazolol4,5-b]pyridm-2(3H)'one. The mixture is stirred for 2 hours at g Ha 2 C and the by now clear solution is concentrated in 21 i rotary evaporator. The crystalline residue IS stirred Compounds melting point 0.0-dieth l-S-loxazolol 4.5-hlp) ridin-Z( 3H onyH 3t-methyll-thiophosphate 38 39 0.0-L|i-isopr0p}l-S [oxaz0lo[-1.5-h]p ridin-2 (3H }-onyl-( 3 l-methyll-dithiophosphate 6| 63 O-rliall \l-S-[ oxazolol 4 5-b}p \ridin2( 3H onyl-i 3 )meth \'l l-tlithiophosphate 48 5U 0,0his-( 2 'chloroelhyl )-S-[oxuzolo{ 4.5-[1 ]-p ridin-2( 3H l-onyl-l 3 )-meth \l]dithiophosphate 6K O-methyl-S-[0xazol0[-l.5 h lp ridin-2l 3H )-onyll3 )-methylj Llithio-phenyl-phosphonate 95 97 0.0di-isopr0p \l-S-[6chloro-omzolo[45-h]- p ridin-Zi 3H )-on I-( 3 Lmethyl l-dithiophosphate 43 45 0.0-his-( 2 -meth0,\} eth )-S-[ fi chloro-oxazolo [4.5-l7lpy ridin-2( 3H )-onyl-( 3 )m cthylhlithionon-distillphosphate ahle oil 0.0-dialll \l-S-[ o-chlorowwazokfl 4.5-hlp ridin- 2( 3Ht-onyl-( 3 Lmeth l]-dithiophosphate 2H 29 O-eth \l S-[(i-chloro-omzolol4.5-h1pyridin-2- t 3H )-onyl-( 3 )-meth l]-dithiophenylphosphonale (1h (18 0.0-dieth l-S-{h-bromo-oxazolol4.5h1pyridin- 2( 3H )-onyl 3 J-methyl lhiophosphate 58 60 0.0-bis-( 2"methos -eth l )-S-| (1hromo-oxazolo- (3H )-onyl-( 3 )-methyl]-dithio-methylphosphonate 5h 58 Calc. 36.40 H 4.23 N 653 S HHS Cl 8.27% ++Found 363 4.3 6.8 l4.. SLlCi fi-i-Calc. C 32.99 H 3.84 N 5.9] S [3.55 Br l6 88/i Found C 33.l H 3.8 N 5.9 S I31) Br I755 with cold water. filtered, and the filtrate crystallised Compounds melting point 0.0-dimethyl-S-I oxamlol4.5-b]pyridin-2( 3H lon l-( 3 l-methylI-thiophosphnte 77 79 2( 3H bony l-( 3 lmeth)Il-dilhiophosphate 83 85 O-methyl-N.N-dimethyl-SloxazoloHj-blpyridin- 2( 3H )-onyl( 3 l-methyll rlithiophosphorus umidate 44 46 p ridin-2( 3 H I-onyl-( 3 )methyl j-dithiophosphorus non-distillumidate able oil-H-i- OO-dimethyLSJ oxuzolo[4.5-hIpyridin-2( 3H I non-distill- -contmued Compounds melting point 0.0-diethyl-S-l oxazolol4.5-hlpyridin-2t 3H onyl t 3 1-1 2'-hromo-eth \'l 1-( l 'll-dithiophosphate 30 32 0.0-diethyl-S h-nitro-oxazolol 4 .S-hlpyrid'm- 2( 3H1-onl-l 3 I-ethyl-t l 'll-dithiophosphute 103 105 -H1-Calc. C 35.92 H 4.ll N HA3 P 8.44 5 17.44 (19.6471 Found C 36.2 H 4.l N ll.5 P 7.9 S l6." Cl 10.0% Male. C 37.49 H 4.09 N 8.75 P 9.69 S 20.0291

Found C 37.6 H 4.1 N 8.5 P 9.6 S 20.4%

Compounds melting point Omethyl-S-( oxazo|o(4.5-h 1p} ridin-Zt 3H l-one 3-yl-melh lJ-dithio methylphosphonate 74 7b Oethyl-S-(o\'.11olol 4.5-l1 lpyridin-Zl 3H )onenon-distill- 3-|meth \l)-dithio-meth}lphosphonttte ahle oil -H--+ll- O-methy l-S-( b-chloro-oxazolot 4.5-h l-pyridin- 2( 3H Lone-3 l-methyl l-dithio-ethylphosphonate 55 56 0.0-dimeth \'l-S-(oxuzoloHfi-h 1p ridin-2t 3H I (4.5-h Jp ridin-2( 3H I- one-R-yl-t Z'chloroethyl l-l l'll-dithiophosphute 66 68 ().O-dimeth \'l-S[ 6-chloro-oxazolot 45-h )-ph ridin- 2[ 3H )-one-3- \l-( 2'-hromoeth \'l l ))-Llithionon-distillphosphate ahle oil -H-++-H- 0.0-dimeth l-S-t fi-hromo-oxazolot 4.5-h lpyridin- 2| 3H )-one-3- \l-( 2'-bromoeth \'l1-( l))-dithionon-distillphosphate ahle oil ++l-+| Calc.: C 39.47 H 4.3l N 9.2] P llLlS 5 21.08% Found 39.5 4.6 8.8 ltl.3 20.89? ++++-H-Callc C 27.69 H 2.56 N 6.47 P 7J6 Cl 8.18 Br 18.43% Found 28.2 2.6 6.5 7.1 7.9 [8.89; -+l+-++-+-+Cz|lc C 25.l2 H 2.32 N 5.86 P 6.49 S l3.4l Br 33.44% Found 25.9 2.5 5.6 (Ll l2.8 33.371

EXAMPLE 23 EXAMPLE 25 548 Grams of 3-chloromethyl-6-chloro-oxazolol4,5- b] pyridine-2(3H)-one. 480 g of the ammonium salt of 0.0-dimethylmonophosphoric acid and 1200 ml of methanol are heated to the boil as quickly as possible while stirring thoroughly and refluxed for 5 minutes. The mixture is poured into 1800 ml of water and the bulk of the methanol is distilled off in a rotary evaporator. The initially oily precipitate congeals in the process to a crystalline state, is isolated by filtration and recrystallised from a mixture of I200 mlof methanol and 300 22 Grams of 3-chloromethyl-6-chloro-oxazolo[4,5 b]pyridine-2(3l-l)-one and 20 g of the sodium salt of O-ethyl-thiophosphoric acid containing water of crystallisation are refluxed for l0 minutes in ml of methanol. The solvent is distilled off in a rotary evaporator and on treating the residue with 100 ml of water a Crystalline filling is obtained. Recrystallisation from 200 ml of aqueous methanol yields l7 g of 0-ethyl-S-( o-chlorooxazolo(4,5-b)pyridin-2(3H)-one-3-yl-methyl)- thiophosphoric amidate (m.p. from 1 10C with decomp.

Calc; C 33.39 1-1 3.43 N l2.98 P 9.59 s 9.91 CI 10.9501 Found: 33.72 3.55 12.91 9.37 9.x9 1 1.070;

ml of water. to yield 497 g of 0,0-dimethyl-S-( 6-chlorooxazolo (4.5-b)-pyridin-2(3H)-one-3-yl-methyl)-thio- 50 EXAMPLE 26 phosphate (mp. 8990C) a. Proceeding in a manner analogous to that de- Cale: c 33.29 H 3.11 N 8.63 P 9.5 $9.88 Cl 10.92% Found: 33.50 3.13 8.52 9.6" 9.711 1 1.115%

EXAMPLE 24 scribed in Examples l8a and 20a, 3-(l',2'-dibromoe- 32 Grams of 3-( l ,2'-dibromoethyl)-oxaz0lo(4,5- myFabmmooxazolm45 b?pyridin'2(3H)'One b)pyridine-2(3H)-one are introduced into a solution of g fgp g g from g2Z"gZ 19 g of the ammonium salt of 0,0-dimethyl dithiophos- Fons T phoric acid in 50 ml of water. The mixture is stirred for one half hour at 70C so vigorously that the fused Calm c 2395 H L25 Br 6w N mm dlbromo compound is well emulsified. The oil layer Found: 24.1 1.2 59.0 7,191 congeals to a crystalline state on cooling and after recrystallisation yields 26 g of 0.0-climethyl-S-(oxazolo (4,5 -b)-pyridin-2(3 l-l)-one-3-yl-(2 '-bromoethyl-(l dithiophosphate (m.p. C), which is identical with the compound of Example 18b.

tassium salt of 0.0-diethyl-dithiophosphoric acid are suspended in 50 ml of methanol and refluxed for minutes. The solvent is then distilled off in a rotary evaporator and the residue is treated with lOO ml of water. The viscous oil that has separated out is taken up in ether. the ether solution washed with sodium bicarbonate solution and water. dried. and the ether distilled off. Sl Grams of 0.0-diethyl-S-(6-bromo-oxazolo(4,5- b)pyridin-2( 3H )-one-3-yl-( 2 "bromoethyl)-( 1 '))-dithiophosphate are obtained in the form of a pale yellow. viscous, non-distillable oil.

26 ture of IO ml of water and ml of methanol. The two solutions are combined and left to stand for 24 hours at room temperature, in the process of which an oily and a crystalline precipitate occur. The mixture is then heated briefly to 60C, the bulk of the methanol is evaporated off in a rotary evaporator, the residue is treated with water and extracted with ether. Recrystallisation from ml of methanol yields 13 g 0.0-diethyl- S-( oxazolo( 4,5-b )pyridin-2( 3H )-one-3-yl-( 2 '-chloroel0 thyl)-l( l '))dithiophosphate (m.p. 4748C).

Cale: C 28.47 H 2.9% N 5.54 P 6.13 S l2.67 Br 3|.59u Found: 1'9.l 3.l 5.6 6.1) IIA 31.1 A

Cale: C 37.64 H -l.2l N 7.32 P 8.ll 5 16.75 Cl 9.2a Found: 37.48 4.37 7.34 107 lb.7| 9.50

EXAMPLE If the same reaction takes place in acetonitrile ina. Chlorine gas is introduced while cooling with ice at l 0C into a solution of 243 g of 3-vinyl-oxazolo[4,5- b]pyridin-2( 3l-l)-one and 0.6 g of hydroquinone in l500 ml of carbon tetrachloride. The reaction solution is then filtered clear and concentrated in a rotary evaporator. The initially oily residue is stirred with petrostead of in aqueous methanol over 4 hours at C. the same product is obtained in poorer yield and purity (m.p. 45-47C).

EXAMPLE 28 By proceeding in a manner analogous to that described in Example l4. 38 g of 0-ethyl-dithio-ethylleum ether until it has thoroughly crystallised. The 30 hos honic i are t d ith 44 f 3- P P g crystalline product 15 then filtered off and 220 g of yl 6 hl l [45 b]pyridine 3(3H) One.36 I z'dlchloroethyn'oxazolgfii5'b)Pyridm'2(3 Grams of 0-ethyl-S-( 6-chloro-oxazolo( 4.5 -b )pyridin one are obtamed -P' 5862 2(3H)-one-3-yl-methyl)-dithioethylphosphonate are obtained (mp. 40-42C).

Calc.: C 37.44 H 4.00 Cl L N 7.94 s l(l l8 P 8.770: Found; 37.28 4. 5 l().22 $.04 I736 8.660}

EXAMPLE 29 Determination of the anthelminthic action in hens infected with Ascaridiu gal/i l to 3 days old chicks are artificially infected with eggs of Asc-uridzu galli (roundworms). Groups of chicks Cale C 41.2 H .5 Cl 30.47 N lllllr/t' each were used per test. Four to five weeks after the Found: 40.9 2.6 30.4 12.0 ,4

Calc.: .8 Found: 3 1.6

b. 12 Grams of 3-(1',2-dichloroethyl)-oxazolo(4,5- b)pyridin-2(3H)-one are dissolved in 40 ml of methanol by gentle heating. l3 Grams of the potassium salt of 0.0-diethyldithiophosphoric acid are dissolved in a mixchicks had been infected. the active substances were administered in 1 dose per day on 3 successive days. Infected chicks that were not treated were used for control purposes. Evaluation The number of Ascaridia gallia rejected per test group over the course of 5 days after the first admini-- tration of active substance was determined daily and the number still found in the intestine of the fifth day was likewise determined on dissection. Furthermore. the number of chicks free from worms was determined.

Daily dosage Number of ascaridia of 5 chicks Number of in mg per kg worm-free body weight rejected during period found chicks of test on disabsolute in 7: of 10 section number tal number 0.0-di-isoprop \l-S-[oxazolo[4.S-hlp) ridin-Zl 3H J-onyH 3 l-methyll-di- 750 68 U S thiophosphate 0.0-his-( Z '-chloroethyl l-S-[oxazolo -continued Acme substance Dail dosage Number of uscaridia of 5 chicks Number of in mg per kg worm-free bod eight rejected during period found chicks of test on disahsolute in 'i of tosection number tal number [-LS-hjmridin-Zt 3H )-on \l-l 3 t-meth xll- 75a 56 Hit) U 5 dithiophosphate 0.0-dieth}l S-[h-chloro-oxaLolo-l45-h] pyridin 3H |-on l-( 3 I-methfll-dithio- 750 75 I t) phosphate (lo-dicth} l-S-[ fs-hromo-ouizolo-l45-h]- p ridin-Bt 3H lon l-I 3 tmeth l dithio- 75H 82 IUU (I 5 phosphate EXAMPLE 3() -continued Tests on mice infected with S p/tacit! ()[Jlt]. and 5 S M qulae p" dubms Actne substance Flies toes flies Five mice each infected simultaneously with oxyurae thiophosphatc (Svplmciu 0l)\l.) and trichostongvlidae (Nenmwspirt 4 I v y f I d d I (4.5-l1ll-Zt3H)-one-3- l- 6U" HI ones cu nus ere rec) e 1t ee mea containing mchy]Fmmphmphm 0.2% of active substance. The mice were dissected on i jh I l 5 i the sixth day of the test and the number of worms pres- 'QB E LQRZ W 0 eat in the intestine was counted. Untreated mice that fig CLO-dimethfl-S-tfi-chloro were simultaneoush infected in the same wav were .i

3-} lmethyl -d|th|ophosphate for LOntrOl P 'P 0.0-dimethylS-(6-chloro4oxa- Active substance Dail} dossage Total dosage Infection of test Infection of the conin mg/kg in mg/kg animals on distrol animals on dissection section 0.0diethylS-I oxaaolol -h p ritlin-Zt 3H )-on \l-l 3 meth \l] 2H8 I248 SypIuu-iu ()IH'l'l. Sypllut'iu uhn-I. dithiophosphate U-U-U-(I-U l-l-Z-J XvmulmpimIu/r. .\'r'mum.tp|'r, dub,

U-O-tJ-U-U (3-8-8- l1) ().O-diethyl-S-loxamlo[-l 5-b]- p ridin-I( 3H )-thione 3 lmeth \l]-dithiophosphate I75 I051) .Syp/zuciu u/Jwl. S p/tuna "In-v1.

lIJl-(l-(l-U ll1--l .\'umuluspir. duh. Ncllmmipir duh. (l-ll-UUU 6-8-3- lU EXAMPLE zolo-(Jj-b)i-pyridinQUHl-one 24" 5" 90' a. Insecticidal contact poison action -I" 0.0-dtmeth l-S-( b-chlortH o\ aa For the test on polyvalent resistant house flies, 4 5- y fl i q gur so 45' n mosquitoes (Aedes uegypti) and stable flies (Stu!n0.\' \'.s' 45 -z-g wit m ggz fi f t le -C or- OX- calcttrmzs), coat mgs of active substance from acetonic 20M 451,]ymridimzmmfime W active solutions in Petrt dishes are applied in the followg-grgethyl)th:ophosp:;ite iisopropy-S(f1-c oromg concemmqons- (oxazoIo-l4.5-bIl-pyridini Z" 60' a. 10 mg active substance/dish (for Musca) s (3H)-one-3- \'l-meth \'|)-dithiob. 1 mg active substance/dish (for Aedes) Fhmplmle O-eth) l-St h-chloro( oxazolo c. l g active substance/m- (for Stomoxys) my After 1 hour the dishes are filled with the test SUlJJGCIS. i u' p I p onate The follovi mg table indicates the time after which all o o dimethyl s(b hmmu(ommlo sub ects are on their backs. (4.5-bl)-p \ridin-2(BHJ-one- 3-\'l-meth\'l)dithio hos hate 5" 5" l0 P P 0.0-dimeth 'l-S-( h-bromo-( ox azolo(-l .5-ht)p ridin-3(3H)-one 2" 2" 3t! MOS- 3- \'l-meth l -lhiophosphate qui- Stable (LU-diethyLS-t bl1f0mfi(OXiJZ0lU Active substance Flies toes flies (45-h) )-p \riding-2[ 3H)-one3- 2" 5" 90' yl-methyl )-thiophosphate 0.0-dimethyl-S-(oxazolo y (,0 (-LS-bl )-p ridin-2( 3H )-one- 14" It] 2- \l-meth \'l)-dithiophosphate i tfitzgimeth l -s-i o x a c l 1h a 20 mg of a 17: dusting agent are uniformly distribt net L f i :f uted In Petri dishes. The dishes are then filled with pliate cockroaches (Phyllodromia germanica and Periplaneta 0.0-dieth \'l-S-(oxazolo(4.5 5 hbpyridinm 3H Hmcdib t americana) and kept under normal conditions at The following table indicates the time after which all animals are in the dorsal position.

Glass 8 days flies mosquitoes Wood 8 tlkl)$ mosquitoes flies stable Hill 3 -yl-methyl )-thiophosphate OvO-dieth l S-( 6-bromo-( oxaphate a Grain weevils are sprayed with 2 ml of V7: acetonic active substance solution from a distance of 10 cm by means of a spray jet. Immediately after the application the weevils are transferred to clean Petri dishes and kept at 22C. The following table indicates the time after which all the weevils are in the dorsal position.

Insecticidal contact poison action against grain weevils:

I l o action. The test lS carried out at -4 C and 70% relame d atmospheric humidity.

The following table indicates the time in days after -r' i' p p which l()% of the aphids are in the dorsal position.

EXAMPLE 32 Acaricidal action a. Action against mites ('Iemmychus urricae) To test 3 10 the acaricidal action, bean leaves that are attacked by adults, encystments and eggs of the red spider mite 2( 3H )-one-3-yl-eth l-( l'll-dithiophosphate l O O-dimelh l-s-mxu lm4 5.h mm. (Tcn'unyclms umcae) are treated with an aqueous p p 3 emulsion containing the test substance in a concentra- Q ggg I tron of 0 .l 7c. The test sub ects are stra ns of the red 04.24 m z' Ten n a-em l I-SJIUXaZUhiI l5 spider mite that are resistant to commercially available I)p r|tinl-one'. -meth 3 dithiophosphate phosphorous esters.

Encysb Adults merits Eggs d, lnsecticidal ingested poison action Potato plants are dipped in a U.l7r aqueous active i lfm g x7 substance emulsion (obtained from 10% emulsifiable it liidghiisphaii mew)- um um concentrate). After the coating has dried. larvae of the gfl fl' colorado potatoe beetle (Leptinotarsa decemlineata) mm'm'zi3Hl'one4'yhelhfl' Hm mu are applied to the plants.

The following table indicates the times in minutes and hours after which all beetles are in the dorsalt position.

dipped for 3 minutes in an aqueous emulsion of active substance in a concentration of 0.1 7:. The ticks are then kept at 27C and 80% relative atmospheric humidity. On the fifth, tenth and fifteenth day. oviposition is determined. The eggs are kept for a further 20 days under the same conditions and the possible hatching rate determined.

Acti\ e substance Tick strain oviposition Hatching rate Ridgeland Biarra Biarra Biarra Biarra Ridgeland Rid gelantl Ridgeland Ridgeland Biarra Biarra Biarra Rid geland Biarra Ridgeland Ridgeland normal normal What we claim is: l. A compound of the formula wherein R is hydrogen, chlorine, bromine or nitro.

R is hydrogen. methyl, chloromethyl or bromomethyl,

R is amino or dialkylamino having a total of from 2 to 4 carbon atoms,

R, is alkyl of from I to 4 carbon atoms, alkenyl of from 2 to 4 carbon atoms alkoxyalkyl having a total of from 2 to 4 carbon atoms, or halogenalkyl of from 1 to 4 carbon atoms, and

each of X and Y represents oxygen or sulphur.

2. A compound according to claim 1 of the formula Cl I c=o I /OCH3 ca s-1 mm s we 

1. A COMPOUND OF THE FORMULA
 2. A compound according to claim 1 of the formUla 